Extracorporeal phototherapy (ECP) is a therapeutic approach based on the biological effect of psoralen 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) on mononuclear cells collected by apheresis, and reinfused into the patient. Photopheresis is widely used for the treatment of patients with advanced cutaneous T-cell lymphoma (CTLC). Evidence suggests that it prolongs life, and also induces 50-75% response rates. In addition, more and more reports indicate that photopheresis is a potent agent in the therapy of acute allograft rejection among cardiac, lung and renal transplant recipients. There are increasing amounts of data showing that patients with chronic graft versus host disease benefit from this therapy. Likewise, there are indications that there may be a potential role for ECP in the therapy of certain autoimmune diseases resistant to conventional therapy. The mechanism of this treatment is likely due to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. Treatment induces apoptotic death of pathogenic T-cells, and it is postulated that activation of antigen-presenting cells has important effects in this process.